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Biomedical subjects

R Suzuki

Publications and source records attributed to R Suzuki.

At least 73 records · Page 4Linked to original sources

Functional annotation of a full-length mouse cDNA collection.

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

Animals↗

Effect of sepimostat mesilate on experimental venous thrombosis in rats.

Sepimostat mesilate (FUT-187: 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethane sulfonate) is a newly synthesized serine protease inhibitor. In the present study, the oral administration of FUT-187 inhibited stasis-induced venous thrombosis in rats. We supposed that such effect of this compound was caused by its inhibitory effect on coagulation. However, the dose of FUT-187 that was effective at inhibiting thrombosis (10 and 30 mg/kg, po) had no effect on the plasma recalcification time (PRCT), activated partial thromboplastin time (APTT) and prothrombin time (PT) in rats. Therefore, we investigated the fibrinolytic activity of FUT-187 in rat plasma. The results revealed that rat plasma after FUT-187 administration exhibited increased amidolytic activity for a plasmin-, tissue-type plasminogen activator (t-PA)-, urokinase-type plasminogen activator (u-PA)-, factor Xa-, factor XIa- and factor XIIa-sensitive synthetic peptide substrate. On the other hand, the inhibitory effect of FUT-187 in the thrombosis model was not affected by additional treatment with epsilon-amino-n-caproic acid (EACA), a plasmin-mediated fibrinolysis inhibitor. These results suggest that even if FUT-187 enhanced fibrinolysis, it would be independent of a plasmin-mediated fibrinolytic pathway. To characterize the fibrinolytic activity, which might reduce the thrombus weight in the thrombosis model administered FUT-187, we carried out fibrinogen zymography, and clarified that FUT-187 enhanced the formation of a 20-kDa fibrinolytic fragment. Interestingly, this fragment was not affected by t-PA. Consequently, we consider that the inhibitory effect of FUT-187 on venous thrombosis model is caused by fibrinolysis, which is attributable to the 20-kDa fragment, rather than by inhibition of thrombus formation.

Animals↗

Different distribution of c-myc and MIB-1 positive cells in malignant meningiomas with reference to TGFs, PDGF, and PgR expression.

We investigated the expression of transforming growth factors (TGFs), platelet-derived growth factor (PDGF), progesterone receptor (PgR), and c-myc in 20 cases of meningioma of various grades: 17 benign, 2 atypical, and 1 anaplastic. All cases of atypical and anaplastic meningioma were positive for c-myc, whereas all 17 benign meningiomas were negative for c-myc immunostaining. Expression of TGF-alpha, TGF-beta, and PDGF-BB proteins was seen in more than 80% of the meningioma cases and was not restricted to their histological grade of meningioma. PgR was expressed mainly in benign meningiomas. Moreover, the cells expressing c-myc protein were not usually stained by MIB-1. These results indicate that c-myc does not directly work on the proliferation of meningioma cells, and even in homogeneous meningioma cells, there may be many functional variations that lead the meningioma cells to their growth.

Aged↗

Peripheral T/natural killer-cell lymphoma involving the female genital tract: a clinicopathologic study of 5 cases.

Malignant lymphoma of the female genital tract (FGT) is rare. In this study, 5 peripheral T/natural killer (NK)-cell lymphomas (PTCLs) involving the FGT are reported. They include 2 from the uterus and 1 each from ovary, uterus and ovary, and vagina, and were detected between 1996 and 2000. One of the 2 ovarian tumors was bilateral. In all cases, the FGT was the initial site of clinical presentation of disease. Age at presentation ranged from 21 to 52 years (median, 36 years). One case was stage I disease, 2 were stage II, and 2 were stage IV. All 5 tumors were positive for CD3epsilon, and 3 harbored the Epstein-Barr virus, although the detailed immunophenotypic profiles varied. Three were diagnosed as nasal type T/NK-cell lymphoma, 1 as anaplastic large-cell lymphoma (anaplastic lymphoma kinase [ALK]-positive), and 1 as unspecified PTCL of cytotoxic phenotype, according to the forthcoming World Health Organization classification. Four of 5 patients received laparotomy and chemotherapy. Four patients (in stages II and IV) died of disease within 16 months of the initial diagnosis, whereas only 1 patient (in stage I) is alive without disease at 39 months of follow-up. Our experience in this series provided clinically relevant information on diagnosis, treatment, and outcome for extremely rare tumors of the FGT.

Adult↗

Assessment of prognostic factors in follicular lymphoma patients.

Prognostic factors, including clinical, biological, and histological parameters, were assessed for 94 patients with follicular lymphomas at our institute. Follicular lymphomas constituted 7.7% (94/1208) of malignant lymphomas in this study. Eighteen patients were diagnosed with stage I follicular lymphoma, 20 with stage II, 23 with stage III, and 33 with stage IV. The cases of follicular lymphoma were subclassified as: follicular small cleaved cell lymphoma (FSC) in 20 cases, follicular mixed cell lymphoma (FMX) in 59 cases, and follicular large cell lymphoma (FLC) in 15 cases. The patients comprised 49 men and 45 women with a median age of 54 years (range, 25-84 years). The complete response rate was 76.5%, and the median survival time was 13 years. The expected 10-year overall survival and event-free survival rates were 61.9% and 38.2%, respectively. Univariate analysis identified the factors associated with poor survival as elevated serum lactate dehydrogenase (LDH) level (P < .0001), age of >60 (P < .0001), Ann Arbor stage III/IV (P < .01), and Eastern Cooperative Oncology Group performance status (PS) of 2 to 4 (P = .048). Multivariate analysis showed that LDH, age, and PS were independent predictors. After application of the International Prognostic Index (IPI), the 10-year survival rates for the low-risk, low-intermediate risk, high-intermediate risk and high-risk groups were 80.4%, 48.7%, 21.9%, and 0.0%, respectively. The differences among these groups were significant at P < .01. The IPI for aggressive non-Hodgkin's lymphoma was found to be applicable to survival prediction for Japanese follicular lymphoma patients.

Adult↗

CD34+-selected autologous peripheral blood stem cell transplantation conditioned with total body irradiation for malignant lymphoma: increased risk of infectious complications.

Although high-dose chemotherapy with autologous peripheral blood stem cell transplantation (autoPBSCT) has been shown or confirmed to be an effective treatment for high-risk and relapsed non-Hodgkin's lymphoma (NHL), relapse after autoPBSCT remains a serious problem. In a clinical trial to overcome relapse, we adopted a treatment plan in which PBSCs purified in vitro to CD34+ cells to deplete tumor cells (CD34+ autoPBSCT), total body irradiation (TBI) of 1200 cGy, and melphalan, 180 mg/m2, were used as a preconditioning regimen. Eighteen patients with relapsed or high-risk NHL participated in the study. This study compared the incidence of complications following CD34+ autoPBSCT preconditioned with the TBI regimen (n = 10): the TBI group; CD34+ autoPBSCT with the non-TBI regimen (n = 8): the non-TBI group; and unselected autoPBSCT with the non-TBI regimen (n = 19): the unselected autoPBSCT control group. After day 30 posttransplantation, 6 of 10 patients treated with the TBI regimen developed 11 infectious complications in total, compared with only 1 of 8 patients treated with the non-TBI regimen and 4 of 19 patients given unselected autoPBSCT. Two fatal complications occurred in the TBI group, but none occurred in the other 2 groups. The CD4+ lymphocyte count at 1 month posttransplantation was significantly lower in the TBI group than in the unselected autoPBSCT group. These findings suggest that the addition of TBI to the preconditioning regimen for CD34+ autoPBSCT is associated with an increased incidence of severe infectious complications after transplantation.

Adult↗

Central nervous system involvement in pyothorax-associated lymphoma: ring enhancement on CT scan.

A 71-year-old male was diagnosed as having pyothorax-associated lymphoma (PAL), a rare hematological malignancy associated with artificial pneumothorax for the treatment of pulmonary tuberculosis. Because of the low incidence, its clinical features have not been fully clarified. The PAL lesion in this patient disappeared after local radiotherapy and corticosteroid treatment. However, 8 months after the initial diagnosis, he developed a variety of neurological disorders and low-grade fever. Neither recurrence of the primary pulmonary lesion nor nodal enlargement was observed. Immediate magnetic resonance imaging of the brain revealed a ring-enhanced mass, suggesting a brain abscess. However, through a stereotactic biopsy of the brain lesion, infiltration of PAL cells was identified. The brain lesion rapidly enlarged despite intensive radiotherapy, and he finally died of lymphoma progression. This case demonstrates that PAL may progress as a type of extranodal lymphoma, and that brain lesions may produce a ring-enhanced pattern on computed tomography.

Aged↗

Cytotoxic effect of conjugated trienoic fatty acids on mouse tumor and human monocytic leukemia cells.

The cytotoxicity of fatty acids from seed oils containing conjugated linolenic acids (CLN) was studied. Fatty acids from pomegranate, tung, and catalpa were cytotoxic to human monocytic leukemia cells at concentrations exceeding 5 microM for pomegranate and tung and 10 microM for catalpa, but fatty acids from pot marigold oil had no effect at concentrations ranging up to 163 microM. The main conjugated fatty acids of pomegranate, tung, catalpa, and pot marigold were cis(c)9,trans(t)11,c13-CLN (71.7%), c9,t11,t13-CLN (70.1%), t9,t11,c13-CLN (31.3%), and t8,t10,c12-CLN (33.4%), respectively. Therefore, the cytotoxicities of fatty acids from pomegranate, tung, and catalpa were supposed to be due to 9,11,13-CLN isomers. To elucidate the cytotoxicity of these CLN, we separated each CLN isomer from the fatty acid mixtures by high-performance liquid chromatography and analyzed its cytotoxicity. The cytotoxicities of c9,t11,c13-CLN, c9,t11,t13-CLN, and t9,t11,c13-CLN were much stronger than that of t8,t10,c12-CLN. Therefore, the higher cytotoxicity of fatty acids from pomegranate, tung, and catalpa than those from pot marigold would be derived from the different activities of 9,11,13-CLN and 8,10,12-CLN. Since there was little difference in the cytotoxicities of c9,t11,c13-CLN,c9,t11,t13-CLN, and t9,t11,c13-CLN, it is suggested that the cis/trans configuration of 9,11,13-CLN isomers had little effect on their cytotoxic effects. The mechanism of the cytotoxicity of the four fatty acids above may involve lipid peroxidation, because the order of toxicity of the fatty acids was consistent with their susceptibility to peroxidation in aqueous phase. This was supported by the decrease in the cytotoxicity of the fatty acids by addition of butylated hydroxytoluene.

Animals↗

Detection of cyclin D1 overexpression by real-time reverse-transcriptase-mediated quantitative polymerase chain reaction for the diagnosis of mantle cell lymphoma.

The diagnosis of mantle cell lymphoma (MCL) is particularly important for clinical management because of a remarkable prognostic difference between MCL and other types of B-cell lymphoma. In addition to immunohistochemical analysis, we have established a 5' exonuclease-based real-time reverse transcriptase-mediated quantitative polymerase chain reaction (RQ-PCR) method to detect cyclin D1 overexpression for the diagnosis of MCL. The RQ-PCR could detect cyclin D1 overexpression in all nine examined MCL cases, in contrast genomic PCR detected t(11;14) in only two of nine cases. By RQ-PCR the expression of G6PDH was significantly higher in myeloid leukemias than those in B-cell lymphomas (P = 0.018). As a result, cyclin D1/G6PDH ratio ranged from 0.78 to 12.4 (mean, 1.83) in MCL, exclusively higher than those in other B-cell lymphoma (0.00009 approximately 0.16) and myeloid leukemia (0.00011 approximately 0.085). The high expression of cyclin D1 in certain myeloid leukemias was identified to reflect their proliferative activity and not to represent the oncogenic overexpression. The 95% confidence interval of the cyclin D1/G6PDH ratio was 0.29 approximately 11.1 for MCL, 0.014 approximately 0.25 for other B-cell lymphomas and 0.000014 approximately 0.083 for myeloid leukemia, suggesting that a cutoff value can be set at 0.25. The RQ-PCR of cyclin D1 is convenient and especially useful for the diagnosis of MCL.

Biomarkers, Tumor↗

PACAP activates PKA, PKC and Ca(2+) signaling cascades in rat neuroepithelial cells.

Several studies have reported that the PAC(1) receptor (PAC1-R), the specific receptor for PACAP, is expressed at early developmental stages. Here, we describe that the cytosolic Ca(2+) concentration ([Ca(2+)](i)) was increased by PACAP, but not VIP, in a concentration range from 10(-12) to 10(-8) M via the PAC(1)-R in isolated single cells from the rat neural fold. This activation of the cells by PACAP was mimicked by agonists and inhibited by antagonists of the cAMP/PKA and PLC/PKC cascades. These data indicate that PACAP/PAC(1)-R is linked to [Ca(2+)](i) signaling via two G-protein-coupled protein kinase pathways and may thereby play an important role in early neurodevelopment.

Animals↗

Comparison of the effects of MK-801, ketamine and memantine on responses of spinal dorsal horn neurones in a rat model of mononeuropathy.

Selective ligation of the L5/L6 spinal nerves produces a partial denervation of the hindpaw and has proved to be a useful model for studying the mechanisms underlying neuropathic pain. Two weeks after surgery, in vivo electrophysiological studies were performed in sham operated and nerve injured rats and the responses of spinal dorsal horn neurones to controlled electrical and natural (mechanical and heat) stimuli were recorded. The systemic effects of three N-methyl-D-aspartate receptor (NMDA) antagonists, ketamine (1-10 mg/kg), memantine (1-20 mg/kg) and MK-801 (0.1-5 mg/kg) were compared. Ketamine a clinically available NMDA receptor antagonist, produced greater reductions of the postdischarge, thermal (10 mg/kg, P=0.02), and mechanical evoked responses in spinal nerve ligated (SNL) rats (von Frey 9 g, 1 mg/kg, P=0.04; 5 mg/kg, P=0.01; 10 mg/kg, P=0.05; von Frey 50 g, 5 mg/kg, P=0.02; 10 mg/kg, P=0.003). The inhibition of wind-up was comparable in both animal groups. Memantine produced powerful inhibitions of wind-up after nerve injury with little effect in sham controls (5 mg/kg, P=0.02). The postdischarge, mechanical and thermal evoked responses were reduced to similar extents by memantine in both experimental groups. The effects of MK-801 were comparable between SNL and sham operated rats for all neuronal measures (wind-up, postdischarge, thermal and noxious mechanical evoked responses). The differential blocking abilities of these antagonists on the various neuronal responses may relate to the characteristics of their voltage-dependent blockage of the channel associated with the receptor. The favourable side effect profile of memantine supports its potential use for the treatment of neuropathic pain.

Animals↗

The nature and function of mononuclear cells on the resorbed surfaces of bone in the reversal phase during remodeling.

In a reversal phase of bone remodeling many mononuclear cells appear on the resorbed surfaces of bone with characteristic reversal lines as revealed by transmission electron microscopy (TEM). However, these mononuclear cells have been variously hypothesized or reported. The present study examined the TEM features on the resorbed surfaces of three calcified connective tissues, and aimed to clarify the nature and function of the mononuclear cells in a reversal phase. Dentine slices cultured with isolated osteoclasts, human deciduous teeth, and rat mandibles were used in this study. Specimens were fixed, decalcified, and then embedded in Epon 812, and sectioned into 0.1-microm-thick ultrathin sections. The ultrathin sections were stained with uranyl acetate and lead citrate, and then examined by TEM. Many sharply pointed collagen fibrils with striation were observed exposed on the resorbed surfaces of cultured dentine slices, but there were neither cells nor reversal lines. The same features were observed on the root dentine surfaces of human deciduous teeth. Under many mononuclear cells in a reversal phase of remodeling, reversal lines were seen on the resorbed surfaces of rat mandibles, but there were no striated collagen fibrils exposed on the bone surfaces. The alternation of the TEM features on the resorbed surfaces before and after the participation of mononuclear cells in a reversal phase of remodeling suggests the nature and function of these cells: they participate in both degrading the demineralized and disrupted matrix left on the resorbed surfaces and forming reversal lines there.

Animals↗

The initial attachment of cemental fibrils to the root dentin surface in acellular and cellular cementogenesis in rat molars.

To elucidate the initial attachment mechanism of cemental fibrils to the root dentin surface in acellular and cellular cementogenesis, developing rat molars were observed by light microscopy and scanning electron microscopy combined with NaOH maceration. The NaOH maceration was used to observe details of the positional association of cemental and dentinal fibrils during cementogenesis. An initial hematoxylin stained, cementum layer began to form on the root dentin surface with the first dentin mineralization in both acellular and cellular cementogenesis. The initial attachment of cemental fibrils to the dentin surface also began at this point. At the initial attachment the intermingling of cemental and dentinal fibrils occurred only in places. With advanced cementogenesis the initial cementum layer became the fibril-poor cemento-dentinal junction. This suggests that cemental fibrils attach on the initial cementum layer, and not directly on dentinal fibrils, so that the layer results in the fibril-poor cemento-dentinal junction. The present study suggests that an intervening adhesive is necessary for the cemento-dentinal attachment at any stage of cementogenesis in rat molars.

Aging↗

A resin embedding method for transparent teeth with ink-infiltrated pulp cavities.

This study was designed to evaluate whether resin embedded transparent teeth are as convenient to use as classical transparent teeth. For this purpose demineralized human teeth were divided into coronal and radical portions, and pulp tissue was extracted from the pulp chamber and root canals, into which drawing ink was injected. After dehydration, the specimens were made transparent in methyl salicylate and immersed in polyester resin. The divided portions were recombined at the polymerization. The resin embedded teeth maintained transparency and the black-stained pulp chamber and root canals showed morphological details. The resin embedded specimens could be handled manually and observed freely from any angle. Previously, transparent teeth have been observed in transparent media through a capped glass bottle. In this respect the resin embedding method is superior to the classical method. The new method will be helpful for investigating root canal morphology.

Dental Pulp↗

The temporal profile of interactions between sensory information from both hands in the secondary somatosensory cortex.

OBJECTIVE: To elucidate the temporal profile of interactions between sensory information from both hands in the somatosensory cortex. METHODS: Somatosensory evoked fields (SEFs), generated by stimulation applied to the right index finger after a preceding stimulation to the left index finger, were recorded using a whole head-type magnetoencephalography (MEG). The paired electrical stimuli were applied with a stimulation onset asynchrony (SOA) of 50, 100, 200, 300, or 400 ms. RESULTS: The mean SEF intensities in the primary somatosensory area (SI) of five subjects, which were evoked approximately 40 ms after the latter of the paired stimuli, were not significantly smaller than that evoked in the control condition when only the right finger was stimulated. In contrast, SEFs in the secondary somatosensory area (SII), generated approximately 100 ms after the stimuli, were suppressed when the paired stimuli were applied at an SOA of 100 ms (P<0.05, t test). In addition, SEFs at approximately 150 ms after the stimuli were significantly suppressed at SOAs of 50, 100 (P<0.05), 200, and 300 ms (P<0.1). CONCLUSION: Within a time window of approximately 300 ms, sensory information from the left finger significantly affected the SEFs generated by sensory inputs from the right finger. This time window may be required for the integration of sensory input.

Adult↗

Localization of epidermal-type fatty acid binding protein in alveolar macrophages and some alveolar type II epithelial cells in mouse lung.

Almost all alveolar macrophages in the mouse lung were strongly immunoreactive for epidermal-type fatty acid binding protein. At the electron microscope level, the immunoreactive material was localized diffusely in the cytoplasm but not within the nucleus. A certain number of alveolar type II epithelial cells were also immunoreactive for the protein with variable immunointensity, while a substantial number of the type II cells were immunonegative. No immunoreactive interstitial fibroblasts were encountered. Based on the present findings, possible roles of epidermal-type fatty acid binding protein in the host-defence mechanism played by alveolar macrophages are suggested.

Animals↗